1 , Laboratory of Virology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece.

1. MiR-21 can be used as independent prognostic factor for survival and metastasis in urinary bladder cancer. Apostolos Zaravinos1, Jelena Radojicic3, George I. Lambrou2, Dimitrios Volanis1,4, Ioannis Boulalas1,4, Dimitris Delakas4, Demetrios A. Spandidos1. 1, Laboratory of Virology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece. 2, 1st Department of Pediatrics, Choremeio Research Laboratory, University of Athens, 11527 Athens, Greece. 3, Department of Surgical Pathology, Medical Faculty, University of Crete, 71110 Heraklion, Crete, Greece. 4, Department of Urology, Asklipieio General Hospital, 16673 Voula, Athens, Greece. Introduction Urinary bladder cancer is the most common malignancy of the urinary tract, responsible for significant mortality and morbidity worldwide. MicroRNAs (miRs) are short non-coding RNA molecules that post-transcriptionally modulate protein expression. Aim of study Our goal was to correlate the expression of 12 micro-RNAs (miR-10b, miR19a, miR19b, miR-21, miR-122a, miR-145_1, miR-205_1, miR-210, miR-221, miR-222, miR-378-1 and miR-296-5p) with the corresponding expression of FGF2, OPN and VEGFA. Gene expression was correlated with the overall and cancer-specific survival of patients suffering from urinary bladder cancer (BC), as well as with recurrence and metastasis. Materials and Methods Gene expression were acquired by qPCR, from 77 BC specimens. Correlation of the gene expression with survival, recurrence and metastasis was employed by SPSS 16.0. Results High expression of miR-21 correlated with worse overall survival (p=0.0099). Univariate analysis showed that miR-21 and miR-210 can be used as independent prognostic factors for overall survival (p=0.015 and p=0.049, respectively). Moreover, univariate analysis revealed that miR-21 can be used as independent prognostic factor for metastasis (p=0.049). Multivariate analysis revealed that miR-21, miR-210 and miR-378_1 can be used as independent prognostic factors for overall survival (p=0.005, p=0.033 and p=0.012, respectively); miR-21 and miR-378_1 can be used as independent prognostic factors for recurrence (p=0.030 and p=0.031, respectively); and miR-21 can be used as independent prognostic factors for metastasis (p=0.049). FGF2 was positively correlated with the majority of the miRs both in BC and normal tissue (p<0.001). OPN was positively correlated with miR-145_1 (p=0.015) in BC, and with miR-296-5p (p=0.017) in normal tissue. VEGFA was positively correlated with miR-21 in BC (p=0.043), and with miR-205_1 (p=0.045), FGF2 (p=0.004) and OPN (p<0.001) in normal tissue. Table 1. Univariate logistic regression was utilized to assess the potential prognostic factors in overall survival, tumour recurrence and metastasis. Table 2. Multivariate logistic regression was utilized to assess the potential prognostic factors in overall survival, tumour recurrence and metastasis. Figure 1. Kaplan-Meier curves depicting overall and cancer-specific survival (%) of urinary bladder cancer patients, regarding to the expression of 11 miRNAs, FGF2, VEGFA and OPN genes (77 patients). Survival differences were assessed using Log-rank (Mantel Cox). Statistical significance was set at the 95% level (p<0.05). Table 1. Table 2. Spearman’s rank correlation coefficient among microRNA, FGF2, OPN and VEGFA expression levels in urinary bladder cancer and adjacent normal tissue samples. Conclusions FGF2 expression was positively correlated with miR-10b, miR19a, miR19b, miR-21, miR-122a, miR-145_1, miR-210, miR-221, miR-222, miR-378-1 and miR-296-5p MiR-21 can be used as independent prognostic factor both for overall patient survival and metastasis of BC. MiR-210 can be used as an independent prognostic factor for overall survival for patients suffering from urinary bladder cancer. Table 2.